Positron emission tomography is often employed in connection with diagnosis and staging of diseases, such as cancer. In the case of cancer, it is important to evaluate both the primary tumor (if present) and all secondary tumors that may be present due to metastasis during staging. Although the secondary tumors originate from the primary tumor, it is possible for the secondary tumors to differ from the primary tumor (or from each other) in significant ways. For example, the receptor status of secondary tumors may or may not be the same as the corresponding receptor status of the primary tumor. Also the receptor status of the secondary tumors may differ from one secondary tumor to another.
A positron emission tomography system includes an arrangement of many detection units around an imaging subject that can determine the position, energy, and arrival time of incoming high energy photons that result from positron annihilation in the imaging subject. Positron emitting isotopes, such as F-18, can be used to label and track the biodistribution of biologically relevant molecules (“molecular probes” or “contrast agents”) throughout the body using a PET system.
It is convenient to classify molecular probes as being metabolic if they relate to cell metabolism in general (without antibody/antigen selectivity) and as being selective if they include an antibody or ligand that is biologically responsive to cell receptor or antigen status.
In a non-limiting example, metabolic probes are usually small molecules in which F-18 has been used for labeling the molecule. For example, FDG (Fludeoxyglucose (18F)) is a small molecule metabolic molecular probe because it is a glucose analog that is taken up by all glucose using cells.
Selective molecular probes can be used in PET imaging to provide images that relate to abnormal expression of proteins, such as HER2/neu (Human Epidermal Growth Factor Receptor 2), which is over-expressed in about 30% of breast cancers.
Another class of small molecule probes relates to functional or physiological parameters. Emitters such as C-11, N-13, or O-15 can be labeled to molecules such as water, oxygen gas, carbon dioxide gas, and ammonia without modifying the structure or behavior of the molecule.
Lastly, there are classes of small molecule probes that are close analogs of neurotransmitters. F18-DOPA is a small molecule example of a neuro-transmitter PET isotope.
It is often useful to obtain both metabolic imaging and selective imaging when evaluating disease. Metabolic PET imaging provides information on total disease burden, while selective PET imaging can be used to determine the applicability of certain kinds of therapy. For example, monoclonal antibody therapy for cancer is appropriate only in cases where the corresponding receptor is present in the primary and/or secondary tumors. Selective PET imaging can be used to image the relevant receptor status of the tumors.
However, in conventional PET, only one positron emitting radionuclide can be imaged at the same time in a given region of interest in the body, even if different molecular probes having distinct radionuclides are used. This is because the different positron emitting radionuclides all emit positrons which annihilate to provide 511 keV annihilation photons that cannot be distinguished from each other by their energy.
Thus, in order to perform both metabolic PET imaging and selective PET imaging, one conventional approach is to perform two imaging runs in succession, with enough time delay between them to allow the labeled molecular probes of the first imaging run to clear (e.g., a time delay greater than several half-lives of the radionuclide used in the first imaging run). Unfortunately, the need for two imaging runs undesirably increases imaging time and cost. Another known approach is to provide two labeled molecular probes simultaneously, and rely on differing half lives of the radionuclides to distinguish the two PET images. However, such approaches require PET data as a function of time (as opposed to a static image), and also relies on significant assumptions relating to in vivo behavior of the labeled molecular probes. Another method requires the two molecular probes (e.g., Na18F and FDG) to have significantly different biodistributions in the body so that they can be spatially separated. However, in this latter approach there is usually significant spillover between the different biodistributions so that they cannot be truly anatomically separated.
Accordingly, it would be an advance in the art to provide improved PET imaging for disease evaluation.